crossing96/oncoscreening huggingface dataset:
A study in a rat initiation-promotion bladder tumour model demonstrated no promoter/progressor potential of dapagliflozin.	Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is indicated to improve glycaemic control in adults of type 2 diabetes. In nonclinical studies, dapagliflozin was neither genotoxic nor carcinogenic. However, in some clinical studies, an increased incidence of bladder cancer was observed in the dapagliflozin group vs. the placebo. Therefore, this study was undertaken to determine if dapagliflozin can act as a promoter in a 2-stage bladder cancer model in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Rats given BBN (100 or 400 mg/kg, po) twice weekly for 6 weeks in Phase 1 were assigned in Phase 2 to receive daily dose of vehicle, dapagliflozin (0.5 mg/kg, po) or uracil (positive control, 3% in diet) from weeks 8-34. All bladders were evaluated by histopathology. Verifying the validity of the model, uracil increased the incidence of bladder cancer, while dapagliflozin had no effect on the incidence or invasiveness of transitional cell carcinoma. The exposure of dapagliflozin at 0.5 mg/kg/day in rats was 7 times the clinical exposure at maximal therapeutic dose (10 mg). In conclusion, dapagliflozin does not act as promoter or progressor of bladder cancer in a validated bladder cancer model in rats.	bladder
[Expert consensus on treatment of intravesical therapy in non-muscle invasive bladder cancer].	Bladder cancer is one of the common malignant tumors in China. Three-quarter bladder cancer is non-muscle invasive bladder cancer with a high recurrence rate. Intravesical therapy can reduce the risk of recurrence and progression in bladder cancer. According to the recent updates of evidence-based medical evidence at home and abroad, as well as the deepening of domestic experts' research on the diagnosis and treatment of bladder cancer, the consensus has summarized the current intravesical therapy for non-muscle invasive bladder cancer in China, including the indications, contraindications and methods for intravesical therapy, as well as commonly used drugs in bladder cancer.	bladder
Maintenance of the bladder cancer precursor urothelial hyperplasia requires FOXA1 and persistent expression of oncogenic HRAS.	"Tumorigenesis requires accumulation of genetic and epigenetic alterations, some of which drive tumor initiation. ""Oncogene addiction"" describes the phenomenon that (1) well-established cancers are dependent on one mutated oncogene or pathway for the maintenance of a malignant phenotype and that (2) withdrawal of the single oncogenic event leads to growth arrest and/or cancer regression. While oncogene addiction has been experimentally validated in advanced tumor models, its role in tumor precursors has not been investigated. We utilized the requirement of Forkhead box A1 (Foxa1) for transcriptional activation of the Upk2-promoter to temporally control the expression of Upk2-HRAS* oncogene, an inducer of urothelial hyperplasia in transgenic mice. Inducible homozygous knockout of Foxa1 in Upk2-HRAS*/UBC-Cre(ERT2)/Foxa1(loxp/loxp) mice results in reduced HRAS* levels. This led to a marked reduction of urothelial proliferation as evidenced by urothelial thinning, degenerative changes such as intracellular vacuole formation, and reduced Ki67 expression. Reduced proliferation did not affect basal, Krt14-positive cells, supporting the fact that Foxa1-regulated Upk2-HRAS* expression occurs primarily in supra-basal cells. Our results indicate that maintenance of urothelial hyperplasia in Upk2-HRAS* mice depends on continuous expression of Foxa1 and activated HRAS, and that mutated receptor tyrosine kinases, FOXA1 and/or other downstream effectors may mediate oncogene addiction in urothelial hyperplasia."	bladder
Diffusion kurtosis imaging to assess correlations with clinicopathologic factors for bladder cancer: a comparison between the multi-b value method and the tensor method.	OBJECTIVES: To assess the efficacy of diffusion kurtosis imaging (DKI) in differentiating low-grade from high-grade tumors and evaluating the aggressiveness of bladder cancer. METHODS: From January 2017 to July 2017, 35 patients (28 males, 7 females; mean age 63 ± 9 years) diagnosed with bladder cancer underwent diffusion-weighted imaging (DWI) with two types of DKI protocols: (1) multi-b value ranging from 0 to 2000 s/mm(2) to obtain mean diffusivity/kurtosis (MD(b)/MK(b)) and (2) the tensor method with 32 directions with 3 b values (0, 1000, and 2000s/mm(2)) to obtain mean/axial/radial diffusivity (MD(t)/Da/Dr), mean/axial/radial kurtosis (MK(t)/Ka/Kr), and fractional anisotropy (FA) before radical cystectomy. Comparisons between the low- and high-grade groups, non-muscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC) were performed with the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MK(t) and Kr values were significantly (p = 0.017 and p = 0.048) higher in patients with high-grade bladder tumors than in those with low-grade tumors. The MK(t), Kr, and MK(b) values were significantly (p = 0.022, p = 0.000, and p = 0.044, respectively) higher in patients with MIBC than in those with NMIBC, while no significant differences (p > 0.05) were found in other values. The AUC of Kr (0.883) was the largest and was significantly higher than those of other metrics (all p < 0.05) for differentiating MIBC from NMIBC, with a sensitivity and specificity of 81.8% and 91.7%, respectively. CONCLUSIONS: Kurtosis metrics performed better than diffusion metrics in differentiating MIBC from NMIBC, and directional kurtosis and Kr metrics may also have great potential in providing additional information regarding bladder cancer invasiveness. KEY POINTS: • Kurtosis metrics performed better than diffusion metrics in differentiating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC). • Directional kurtosis can provide additional directional microstructural information regarding bladder cancer invasiveness.	bladder
Integrated analysis of (18)F-FDG PET/CT improves preoperative lymph node staging for patients with invasive bladder cancer.	OBJECTIVES: Preoperative (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) is controversial to assess lymph node (LN) staging in patients with invasive bladder cancer. We proposed to use the maximum standardized uptake value (SUV(max)) associated with axial-based LN size to improve the detection of regional LN metastasis. METHODS: From May 2015 to May 2017, we prospectively included patients with urothelial bladder cancer who underwent radical cystectomy with extended pelvic LN dissection. All patients underwent preoperative (18)F-FDG PET/CT staging before surgery. The gold standard comparator was the pathological examination of resected LNs. The data were reported on a regional per area- and patient-based model according to SUV(max) values and axial-based LN size criteria. RESULTS: In total, 1012 LNs were identified in 61 patients with clinically localized invasive bladder cancer who underwent radical cystectomy and extended pelvic LN dissection. Loco-regional involvement of 24 LN areas was confirmed in 17 patients. In per area analysis, diagnostic accuracy of PET/CT and CT alone were respectively 84% and 78% (p = 0.039). On patient-based analysis, combined PET/CT correctly classified pelvic LN status in 5/61 (+ 8%) additional patients using optimal thresholds compared to CT alone, with accuracies of 82% and 74%, respectively (p = 0.13). CONCLUSION: Combining SUV(max) and axial-based LN size criteria using (18)F-FDG PET/CT improved the diagnostic accuracy for preoperative LN staging in patients with invasive bladder cancer, in per area analysis. KEY POINTS: • Combining metabolical and morphological features using(18)F-FDG PET/CT improves the detection of malignant lymph node in patients with bladder cancer. • (18) F-FDG PET/CT may help for initial staging of patients with muscle invasive bladder cancer.	bladder
Randomized Phase 1 Trial of Pembrolizumab with Sequential Versus Concomitant Stereotactic Body Radiotherapy in Metastatic Urothelial Carcinoma.	Preclinical data indicate that radiotherapy works synergistically with pembrolizumab, but the effect and toxicity of this combination may depend on radiotherapy timing. We conducted a randomized phase 1 trial combining pembrolizumab with either sequential (A) or concomitant (B) stereotactic body radiotherapy (SBRT) in metastatic urothelial carcinoma (mUC). No dose-limiting toxicity occurred. Treatment-related adverse events (trAEs; Common Terminology Criteria for Adverse Events v4.0) of grade 1-2 occurred in six of nine and all nine patients in arms A and B, respectively. One grade 3 trAE occurred in arm B. No grade 4-5 trAEs occurred. Overall response rates of 0% and 44.4% were noted in arms A and B, respectively, as per Response Evaluation Criteria in Solid Tumors v1.1. The trial was not powered to compare efficacy between arms. Targeted sequencing of tissue DNA and circulating tumor DNA (ctDNA) revealed high genomic concordance. Treatment response was associated with ctDNA fraction decline. We conclude that sequential and concomitant SBRT can be safely combined with pembrolizumab in mUC and that the effect of SBRT timing on efficacy is worth exploring further. PATIENT SUMMARY: This study assessed the safety of pembrolizumab combined with radiotherapy at two different time points in metastatic bladder cancer. We conclude that the combination treatment was well tolerated.	bladder
[COMPLETE RESECTION OF URACHAL CARCINOMA WITH SIGMOID COLON INVASION AFTER FOLFOX CHEMOTHERAPY: A CASE REPORT].	A 45-years-old man presented discharge of abscess from the umbilicus with lower abdominal pain. CT scan showed huge tumor from the bladder to the umbilical part with sigmoid colon invasion. He was diagnosed as urachal carcinoma, which was confirmed by pathological examination. We started FOLFOX chemotherapy according to advanced colon cancer. Approximately 80% of reduction was accomplished after 11 courses of FOLFOX. We performed radical cystectomy with sigmoid colon resection. Pathological examination revealed complete resection with negative surgical margin. No recurrence and metastasis were observed after 30 months of surgery. Urachal carcinoma is often advanced cancer when diagnosed. Effective chemotherapy is not established well. FOLFOX chemotherapy demonstrated the well antitumor effect in this case.	bladder
Comparison of different prognostic models for predicting cancer-specific survival in bladder transitional cell carcinoma.	OBJECTIVE: To construct the newly valuable nomogram which can compare the predictive performance with American Joint Committee on Cancer (AJCC) staging system in bladder transitional cell carcinoma (BTCC). METHODS: BTCC patients were screened (2004-2015) from the SEER database. The nomogram incorporating lymph node ratio was constructed to evaluate individualized cancer-specific survival. RESULTS: The C-index of the nomogram for predicting cancer-specific survival was 0.743 (95% CI: 0.720-0.766), which was higher than C-index of the AJCC staging system. CONCLUSION: Lymph node ratio can be a reliable prognostic indicator for BTCC. The proposed nomogram showed more satisfactory predictive accuracy and wider applicability than current AJCC staging system in individualized prediction of BTCC patients.	bladder
Patient-reported extremity symptoms after robot-assisted laparoscopic cystectomy.	AIMS AND OBJECTIVES: To describe patient-reported extremity symptoms after robot-assisted laparoscopic cystectomy in patients with bladder cancer. BACKGROUND: Preventive activities for remaining patient safety due to correct positioning play an important part in perioperative nursing care.Extremity injuries are well-known after prolonged surgery, especially in robot-assisted urologic surgery in the steep Trendelenburg position. The risk of injury increases due to patient-related and operative risk factors. METHODS: A quantitative prospective observational study was conducted. Patients were followed up with the QuickDASH (Disabilities in the Arm, Shoulder and Hand), Lower Extremity Functional Scale (LEFS) and a study-specific questionnaire 7-10 days and monthly, up to six months after surgery in patients with extremity symptoms. The study adheres to STROBE (strengthening the reporting of observational studies in epidemiology) guidelines, see Supporting information File S1. RESULTS: Out of the 94 included participants, 46.8% (n = 44) experienced extremity symptoms 7-10 days after surgery. Pain, numbness and weakness were the most frequent symptoms. There was a discrepancy between the patients reported symptoms and the documentation in the patient records. Only 13.6% (n = 3) of the reported pain was documented, respectively 27.5% (n = 11) of other symptoms. CONCLUSION: A large proportion of the patients report postoperative extremity symptoms after robot-assisted laparoscopic cystectomy. Prevention of complications in the perioperative setting, are together with follow-ups, important nursing activities for maintaining patient safety and may both prevent and detect postoperative extremity symptoms and injuries. RELEVANCE TO CLINICAL PRACTICE: This study reveals the need of accurate documentation regarding extremity symptoms in digital patient records, as well as continuous follow-ups during the hospital stay and after hospital discharge to enable detection of treatable extremity injuries. The result of this study also indicates the importance of nursing activities such as evidence-based positioning guidelines in the operating theatre for optimal positioning.	bladder
[Organ preservation in cancer of the upper urinary tract].	Urothelial carcinoma of the upper urinary tract is a rare disease. Tumor biology is comparable to transitional cell carcinomas of the bladder. Local tumor control is much more difficult to achieve in the upper urinary tract than in the bladder. Radical nephroureterectomy is often performed due to carcinomas with low grade histology. Progression rates in these cases are rare; overtreatment has to be discussed. The current article uses the available published data to discuss whether local treatment is an option for tumors of the upper urinary tract. Summarizing the available data, it is indicated that if complete resectability is possible organ preservation is equivalent to radical nephroureterectomy independent of the T‑ and G‑category of the tumor.	bladder
Epigenetic Mechanisms Influencing Epithelial to Mesenchymal Transition in Bladder Cancer.	Bladder cancer is one of the most incident neoplasms worldwide, and its treatment remains a significant challenge, since the mechanisms underlying disease progression are still poorly understood. The epithelial to mesenchymal transition (EMT) has been proven to play an important role in the tumorigenic process, particularly in cancer cell invasiveness and metastatic potential. Several studies have reported the importance of epigenetic mechanisms and enzymes, which orchestrate them in several features of cancer cells and, specifically, in EMT. In this paper, we discuss the epigenetic enzymes, protein-coding and non-coding genes, and mechanisms altered in the EMT process occurring in bladder cancer cells, as well as its implications, which allows for improved understanding of bladder cancer biology and for the development of novel targeted therapies.	bladder
CALD1, CNN1, and TAGLN identified as potential prognostic molecular markers of bladder cancer by bioinformatics analysis.	BACKGROUND: Bladder cancer (BC) is one of the most common malignant neoplasms in the genitourinary tract. We employed the GSE13507 data set from the Gene Expression Omnibus (GEO) database in order to identify key genes related to tumorigenesis, progression, and prognosis in BC patients. METHODS: The data set used in this study included 10 normal bladder mucosae tissue samples and 165 primary BC tissue samples. Differentially expressed genes (DEGs) in the 2 types of samples were identified by GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online website DAVID. The online website STRING was used to construct a protein-protein interaction network. Moreover, the plugins in MCODE and cytoHubba in Cytoscape were employed to find the hub genes and modules in these DEGs. RESULTS: We identified 154 DEGs comprising 135 downregulated genes and 19 upregulated genes. The GO enrichment results were mainly related to the contractile fiber part, extracellular region part, actin cytoskeleton, and extracellular region. The KEGG pathway enrichment results mainly comprised type I diabetes mellitus, asthma, systemic lupus erythematosus, and allograft rejection. A module was identified from the protein-protein interaction network. In total, 15 hub genes were selected and 3 of them comprising CALD1, CNN1, and TAGLN were associated with both overall survival and disease-free survival. CONCLUSION: CALD1, CNN1, and TAGLN may be potential biomarkers for diagnosis as well as therapeutic targets in BC patients.	bladder
Recovery and functionality of cryopreserved peripheral blood mononuclear cells using five different xeno-free cryoprotective solutions.	In this study, we compared three commercially available and two widely used CPAs for their ability of cryopreserving PBMCs. Similar survival (81.0%) and recovery rate (73.7%) were observed among cells using these five CPAs. However, all the cryopreserved PBMCs exhibited a significantly lower survival rate when compared with the fresh samples (94.3%). We further evaluated effector cell subpopulation and tumoricidal activity of PBMC-derived cytokine-induced killing (CIK) cells and natural killing (NK) cells. Similar and high survival (CIK: 88.6%; NK: 87.5%) and recovery (CIK: 99.5%; NK: 99.7%) rates were detected in CIK and NK cells prepared from cryopreserved PBMCs using the five CPAs. The CD3(+)CD56(+) effector percentage (27.3%) of cryopreserved PBMC-derived CIK cells using the five different CPAs and their tumoricidal activities on melanoma CHL-1 cells (45.7%) and bladder cancer cell line T-24 (44.7%) were similar but significantly lower than those of the fresh PBMC-derived controls (effector: 30.7%; CHL-1: 84.2%; T-24: 82.2%). Cryopreserved PBMC-derived NK cells also exhibited similar tumoricidal activities (CHL-1: 73.8%; T-24: 71.9%) but was significantly lower than that of the fresh control group. We were not able to identify a specific CPA that performed superior than others in PBMC cryopreservation.	bladder
Relationship between the expression of PD-1/PD-L1 and (18)F-FDG uptake in bladder cancer.	PURPOSE: Immunotherapy aimed at inhibiting the PD-1/PD-L1 immune checkpoint has been approved and used successfully for the treatment of bladder cancer. The identification of markers predictive of response to immune checkpoint inhibitors is critical to advancing the success of this therapy. (18)F-FDG PET/CT is a molecular imaging technique that can provide phenotypic information on malignant tumours. It is currently unknown whether there is a relationship between (18)F-FDG uptake and expression of PD-1/PD-L1 in bladder cancer. In this study, we investigated whether PD-1/PD-L1 expression is associated with (18)F-FDG uptake in bladder cancer, and whether (18)F-FDG PET/CT imaging can be used to predict the PD-1/PD-L1 status of bladder cancer. METHODS: A retrospective analysis was performed in 63 patients with bladder cancer who had undergone (18)F-FDG PET/CT before surgical resection. Maximum standardized uptake values (SUVmax) were determined. RESULTS: SUVmax was significantly higher in PD-1-positive patients than in PD-1-negative patients (33.0 ± 13.9 and 19.6 ± 14.2, respectively; P = 0.032), and in PD-L1-positive patients than in PD-L1-negative patients (29.1 ± 15.6 and 15.8 ± 11.4, respectively; P < 0.0001). In a multivariate analysis SUVmax was significantly associated with both PD-1 expression and PD-L1 expression (P = 0.021 and P = 0.003, respectively). Using a SUVmax cut-off value of 22.7, PD-1 status and PD-L1 status could be predicted with accuracies of 71.4% and 77.8%, respectively. CONCLUSION: Higher (18)F-FDG uptake by bladder cancer is associated with elevated PD-1/PD-L1 expression. (18)F-FDG PET/CT may be useful for predicting the PD-1/PD-L1 status of bladder cancer and for determining the optimal therapeutic strategy.	bladder
The prognostic impact of incidental prostate cancer following radical cystoprostatectomy: a nationwide analysis.	BACKGROUND: To determine the prevalence and prognostic impact of incidental prostate cancer in patients undergoing radical cystoprostatectomy. METHODS: A nationwide population-based study of incidental prostate cancer diagnosed following radical cystoprostatectomy. Information on vital status, Gleason score, positive and negative tumor margins, pT-category and subsequent prostate cancer therapies were obtained from the Danish Prostate Cancer Registry and by manual chart review. RESULTS: A total of 1,450 men who underwent radical cystoprostatectomy in Denmark from 1995-2011 were identified. Forty-six men were excluded from analysis, thus 1,404 patients were eligible. The median follow-up was 7.8 years. A total of 466 (33.2%) had incidental prostate cancer diagnosed. No statistical differences in 10- and 15-year cumulative overall mortality were observed when comparing men with, or without, incidental prostate cancer. In men diagnosed with incidental prostate cancer, neither Gleason score, positive surgical margins or locally advanced prostate cancer (pT3-4) was associated with mortality. Only 0.9% received post-operative prostate cancer-related treatment. CONCLUSION: In this population-based cohort of patients with incidental prostate cancer diagnosed at radical cystoprostatectomy, we found no impact of incidental prostate cancer on overall mortality, regardless of Gleason score, surgical margin status and pathological T-category. Patients diagnosed with incidental prostate cancer following radical cystoprostatectomy are unlikely to benefit from additional follow-up.	bladder
Population-based validation of the National Comprehensive Cancer Network recommendations for baseline imaging for bladder cancer: a case for routine baseline bone scan?	AIM: This study aims at evaluating the performance of some of the imaging recommendations of the National Comprehensive Cancer Network (NCCN) for initial evaluation of bladder cancer. METHODS: Surveillance, epidemiology and end results program (2010-2015) was queried and patients with clinically (T1-T4) bladder cancer and complete information about clinical T/N (tumor/nodal) stage and metastatic sites were extracted. The following characteristics were evaluated in the current analysis: sensitivity, specificity, number needed to investigate (NNI), positive predictive value (PPV), negative predictive value and accuracy. RESULTS: According to the current NCCN guidelines, PPV (for the recognition of lung metastases) is 4.7% and NNI to detect one case of lung metastasis is 21.2. Similarly, PPV (for the recognition of liver metastases) is 3.1% and NNI to detect one case of liver metastasis is 32.2. Using a different imaging threshold (i.e., routinely imaging all patients >T2N0), PPV (for the recognition of lung metastases) is 10.4% and NNI to detect one case of lung metastasis is 9.6. Similarly, PPV (for the recognition of liver metastases) is 7% and NNI to detect one case of liver metastasis is 14.2. The above two thresholds were also evaluated for routine bone scanning. PPV (for the detection of one case of bone metastasis) is 5.3% using the first threshold and 11.2% using the second threshold. CONCLUSION: Imaging per current NCCN guidelines results in few patients with undetected asymptomatic lung or liver metastases. A routine baseline bone scan should be additionally considered for some asymptomatic patients with muscle-invasive disease.	bladder